The main application of this invention is in the treatment of autoimmune diseases such as rheumatoid arthritis and other inflammatory conditions using a process of “Targeted Apheresis”.
Current methods of treatment of autoimmune disease typically consist of: for mild cases of autoimmune disease treatment usually consists of aspirin or non-steroidal anti-inflammatory drugs. For more severe cases steroidal drugs such as cortisone, prednisone and methylprednisolone are used. Finally, in cases where the patients become unresponsive to these drugs more cytotoxic drugs such as methotrexate and/or immune modulating drugs may be used. In addition to their therapeutic effect these drugs all have a systemic effect and can cause serious side-reactions. It is desirable to have a treatment process that has fewer side effects.
Apheresis is a process where the patient's blood is passed through an extracorporeal device that physically removes the pathogenic substances that are causing the disease symptoms. As apheresis does not involve administering pharmaceuticals there is no adverse systemic effect on the patient. Apheresis is not a cure for the disease; rather it is a treatment modality that can remove certain of the pathogenic compounds that are contributing to the symptoms of the disease and therefore ameliorate disease symptoms for a period of time.
The principle and practice of using apheresis to treat autoimmune disease is well-established. Therapeutic apheresis has been used to treat a variety of autoimmune diseases and immune disorders including: Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Myasthenia Gravis (MG), Guillain-Barre Syndrome, Goodpasture's Syndrome, and Idiopathic Thrombocytopenic Purpura. The conventional method of performing therapeutic apheresis however is very limited and inefficient. For example, current apheresis therapy uses a single process to treat a variety of autoimmune diseases by removing IgG immunoglobulins in a non-specific fashion. This process is inefficient because a large amount of native IgG is removed along with the pathological IgG autoantibodies involved in the autoimmune disease process. Moreover, removing native IgG may stress the patient and increase susceptibility to infection.
Rheumatoid arthritis patients have “altered IgG” in which “hidden” regions of the IgG molecule are exposed. They produce rheumatoid factor (RF) which is an IgM autoantibody that reacts with the altered IgG. This can result in the formation of immune complexes that can deposit in joints, organs and tissues to cause the symptoms of arthritis.
Rheumatoid arthritis patients may also produce IgG class and IgA class RF autoantibodies that can also react with “altered IgG” and cause disease symptoms.
Until recently, there was only one approved apheresis method in the US for treating rheumatoid arthritis.-the Prosorba® Column. The Prosorba® column is an immunosorbent device that contains Protein A covalently bound to inert silica granules. When plasma is passed thru the device the immobilized Protein A binds out IgG class immunoglobulins and circulating immune complexes. The cleaned plasma is then returned to the patient. This process however, is inefficient because it removes native IgG along with the altered IgG and immune complexes, and a typical course of treatment required multiple apheresis procedures to achieve a result. Also, it did little to remove the circulating unbound RF autoantibodies that are also involved in the disease process. There was also some controversy as to whether the observed beneficial effect is due to removal of immune complexes, or to the leaching out of small amounts of Protein A and other compounds which are introduced back into the patient. The Prosorba® Column was withdrawn from the market in 2006 because of lack of demand due to the high cost of treatment; and there are currently no FDA approved devices for treating RA using apheresis.
In view of the shortcomings of current apheresis methods for treating RA, it would be desirable to develop an apheresis method that would be more efficient in selectively removing the immune complexes as well as the unbound RF autoantibodies involved in the disease symptoms of rheumatoid arthritis.
It would also be advantageous if some of the elements thought to be responsible for initiating the RA disease process were also removed. For example; it is believed that “altered IgG” is an initiator for the rheumatoid factor immune response. Therefore removal of “altered IgG” using apheresis could suppress or delay initiation of the autoimmune response. It would be desirable to develop an apheresis method for removing “altered IgG”.
In addition to the pathogenic elements that are characteristic for a particular autoimmune disease such as rheumatoid factor for rheumatoid arthritis there are also other factors that may contribute and/or exacerbate disease symptoms. For example; patients with autoimmune disease produce pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 (IL-1) that may stimulate the autoimmune response and exacerbate disease symptoms. It would be desirable to develop an apheresis method that would remove these pro-inflammatory elements and ameliorate disease symptoms.
This invention teaches a novel comprehensive approach to therapeutic apheresis that employs a method of simultaneously and selectively targeting the removal of only the pathogenic and pro-inflammatory elements involved in the disease process while leaving the normal elements intact. For example, to treat RA this method of “Targeted Apheresis” will remove the pathogenic factors such as RF and immune complexes believed to be directly involved in the disease process; and also remove the pro-inflammatory cytokines such as TNF-alpha and IL-1 that can exacerbate disease symptoms; and also remove factors such as “altered IgG” that can incite the development of the disease process.
The novelty of this invention is the use of a single targeted apheresis affinity device to simultaneously and selectively remove multiple pathogenic and pro-inflammatory factors from the blood of patients with rheumatoid arthritis. The same treatment rationale can be similarly applied to other autoimmune diseases and inflammatory conditions.